Biosensors have been exploited by researchers for many years in the areas of diagnostics and monitoring of diseases, drug discovery, proteomics and environmental monitoring. Fundamentally, biosensors are analytical devices that convert a biological response into a detectable electrical or optical signal. A large amount of biosensor research efforts have been devoted to the evaluation of the relative merits of various signal transduction methods such as optical, radioactive, electrochemical, piezoelectric, magnetic and micromechanical.
One of the known signal transduction devices used for biological applications includes optical spectroscopic devices, such as Surface Plasmon Resonance (SPR) devices, which provide a label-free, real-time measurement of a substance by using an optical method that detects changes in the refractive index of a dielectric film adjacent to a metal surface. However, in the era of nano-scale research, the use of SPR for nano-scale biological applications is particularly limited. A variety of auxiliary optical structures are usually required to induce SPR (including a prism, grating, or waveguides). In this regard, due to the difficulties involved in assembling these auxiliary optical structures in a miniaturized scale, known miniaturized SPR devices do not usually have an integrated conduit for the liquid sample. Accordingly an independent flow cell has to be used. This results in a constant need to arduously align the flow cell with the miniaturized SPR devices before each operation.
In view of the above, the ability of localized surface plasmon resonance (LSPR) spectroscopy to be employed in biological applications is increasingly important and has been demonstrated by several research groups. The phenomenon of localized surface plasmon resonance is caused by certain unique properties of noble metal nanoparticles. Noble metal nanoparticles exhibit a strong UV-visible absorption band that is absent in the spectrum of the bulk noble metal. This absorption occurs when the incident photon frequency is resonant with the collective oscillation of the conduction electrons in the nano-metal particles, resulting in LSPR. Similar to SPR which is already widely used by biologists, LSPR is also an effective tool to characterize the biological interfaces, and has ten times higher sensitivity than SPR within its electromagnetic decay length of 5-15 nm. This makes LSPR quite suitable for monolayer molecular or short-chain DNA detection.
As compared to SPR, which utilizes a noble metal film and requires auxiliary optical structures (either prism, gratings, or waveguides) for it to function, LSPR can easily be measured through a normal UV-vis-near-IR spectroscopy, by the absorption spectrum of noble metal (silver or gold) nanostructures. Furthermore, the peak of the LSPR spectrum is tunable according to the shape and size of the metal nanostructures.
Currently LSPR has been confined to applications involving laboratory research. Known methods used in the fabrication of micro/nanofluidic devices are not suitable for LSPR device fabrication. For example, the use of anodic bonding at high temperatures may damage the nanostructures, which are important components required for LSPR generation. Moreover, the glass etching technique, which is commonly used in micro/nanofluidic device fabrication, will roughen the surface of the glass wafers and cause a lot of unwanted scatterings in LSPR.
There is a need to provide a sensor chip that overcomes, or at least ameliorates one or more of the disadvantages described above.
There is a need to provide a sensor chip for detecting LSPR on a miniaturized scale, that would meet any one or more of the following criteria: is biocompatible, robust, cost-effective, transparent with minimum light scatterings, has an integrated conduit that contains the fluid sample and can be fabricated through mass production.